Chemical mustard containment using simple palladium pincer complexes: The influence of molecular walls

Article abstract of DOI:10.1021/ja408770u

Six amide-based NNN palladium(II) pincer complexes Pd(L)(CH₃CN) were synthesized, characterized, and examined for binding the sulfur mustard surrogate, 2-chloroethyl ethyl sulfide (CEES). The complexes all bind readily with CEES as shown by ¹H NMR spectroscopy in CDCl₃. The influence of para-substituents on the two amide phenyl appendages was explored as well as the effect of replacing the phenyl groups with larger aromatic rings, 1-naphthalene and 9-anthracene. While variations of the para-substituents had only a slight influence on the binding affinities, incorporation of larger aromatic rings resulted in a significant size-related increase in binding, possibly due to increasing steric and electronic interactions. In crystal structures of three CEES-bound complexes, the mustard binds through the sulfur atom and lies along the aromatic walls of the side appendages approximately perpendicular to the pincer plane, with increasingly better alignment progressing from phenyl to 1-naphthalene to 9-anthracene.

Full text of DOI:10.1021/ja408770u

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Article
Chemical Mustard Containment Using Simple Palladium
Pincer Complexes: The Influence of Molecular Walls
Qi-Qiang Wang, Rowshan Ara Begum, Victor W Day, and Kristin Bowman-James
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja408770u • Publication Date (Web): 04 Oct 2013
Downloaded from http://pubs.acs.org on October 6, 2013
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Chemical Mustard Containment Using Simple Palladium Pin-
cer Complexes: The Influence of Molecular Walls
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QiꢀQiang Wang, Rowshan Ara Begum, Victor W. Day, and Kristin BowmanꢀJames*
Department of Chemistry, University of Kansas, Lawrence, Kansas 66045
Supporting Information Placeholder
ABSTRACT: Six amideꢀbased NNN palladium(II) pincer complexes Pd(L)(CH3CN) were synthesized, characterized, and examꢀ
ined for binding the sulfur mustard surrogate, 2ꢀchloroethyl ethyl sulfide (CEES). The complexes all bind readily with CEES as
shown by 1H NMR spectroscopy in CDCl3. The influence of paraꢀsubstituents on the two amide phenyl appendages was explored
as well as the effect of replacing the phenyl groups with larger aromatic rings, 1ꢀnaphthalene and 9ꢀanthracene. While variations of
the paraꢀsubstituents had only a slight influence on the binding affinities, incorporation of larger aromatic rings resulted in a signifꢀ
icant sizeꢀrelated increase in binding, possibly due to increasing steric and electronic interactions. In crystal structures of three
CEES bound complexes, the mustard binds through the sulfur atom and lies along the aromatic walls of the side appendages apꢀ
proximately perpendicular to the pincer plane, with increasingly better alignment progressing from phenyl to 1ꢀnaphthalene to 9ꢀ
anthracene.
Introduction
Interest in the chemical mustards began as a result of their toxic
Scheme 1. Amide Substituents in the NNN Pincer Skeleton
properties and use as chemical warfare agents in World War I.1
Hence, in the early half of the 20th century considerable
research was directed toward unraveling the complex chemistry
of these harmful agents.2 Yet findings that they also have value
in therapeutical applications, particularly the amineꢀbased
mustards, such as in chemotherapy first in the 1940s3 and more
recently as well,4 have revived interest in their chemistry.
The original mustard gas, 2,2’ꢀdichlorodiethyl sulfide, has a
number of variants, including the nitrogen mustards, 2,2’ꢀ
dichlorodiethylamines, and the half sulfur mustard, 2ꢀ
chloroethyl ethyl sulfide (CEES).2 Much of the chemistry of the
mustards involves the electrophilic nature of the βꢀCH2 groups,
which undergo either intramolecular or intermolecular
nucleophilic attack.2,5 Consequently, these reactive molecules
can alkylate important cellular components such as DNA, RNA
and proteins, which leads to their cytotoxicity.6
While considerable research has been devoted to exploring
ways to decontaminate the mustards,7 current efforts also focus
on their medicinal potential.8 Hence, timely challenges include
both a better understanding of mustard chemistry and the
development of efficient artificial receptors for their detection
and decontamination as well as for binding and delivery.9ꢀ11
In the course of developing receptor systems for the half
sulfur mustard, CEES, with palladium(II) pincer complexes, we
uncovered significantly enhanced binding when naphthalene
and anthracene walls were used to align with the bound linear
guest. In short, extended aromatic side appendages provide
effective containment for the pseudoꢀlinear CEES guest
(Scheme 1).
Pincer ligands are relatively rigid tridentate chelates typically
composed of a central donor atom from a phenyl ring or other
heterocycle (e.g., pyridine) plus two side orthoꢀsubstituted
donor atoms.12 Pincer complexes with a variety of transition
metal ions have been of broad interest because of their versatile
chemistry, including applications in catalysis, sensing and
materials research.12ꢀ14 The key to the reactivity of these
complexes lies in the general lability of the fourth coordination
site. Upon initial isolation, the fourth site is usually occupied
by a counterion or solvent molecule, which can be replaced by
a stronger ligand.15ꢀ18
Recently we reported SNS thioamideꢀbased platinum(II)
pincer complexes as proton switches for the half sulfur mustard
(CEES), along with preliminary studies of the amideꢀbased
system reported here.19 The SNS platinum(II) complexes
undergo reversible thioamide ↔ iminothiolate transformations
with base followed by acid, which accordingly leads to the
reversible binding
coordination site.
↔ release of CEES at the fourth
Preliminary studies, including a crystal structure, on a
corollary amideꢀbased NNN palladium(II) pincer revealed that
it also binds CEES, but without the switchꢀlike mechanism.
Because of the relative synthetic ease of synthesizing modified
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ing that the cyclization process does not occur, most probably
due to the steric bulk of the expanded aromatic systems (see
Supporting Information).
appendages in this class of ligand systems, we decided to
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explore the electronic and steric influences of the ligand
periphery on CEES binding. Herein we report the structural and
binding results, along with the unanticipated binding
enhancements afforded by peripheral “walls.”
Scheme 2. ChemDraw Depiction of the Binding of CEES with
Pd(La)(CH3CN) Showing Hꢀatom Assignments for CEES
Results and Discussion
Synthesis
The N,N’ꢀdisubstituted pincer ligands, H2L, were synthesized
by reacting 2,6ꢀpyridinedicarbonyl dichloride with two equivaꢀ
lents of the corresponding amines in high yields (70ꢀ92%) usꢀ
ing commonly accepted procedures.14,19 The synthesis of the
NNN palladium(II) pincer complexes Pd(L)(CH3CN) is
straightforward by reacting H2L with 1 equivalent of Pd(AcO)2
in acetonitrile at room temperature for several days as reported
previously (see Supporting Information).16,19 After the reaction,
the products were directly obtained by filtration and recrystalꢀ
lized from acetonitrile if necessary to give pure compounds in
51ꢀ99% yields.
The CEES complexes used for the studies were obtained in
two different ways. For the binding studies, the precursor comꢀ
plexes were dissolved in CDCl3 followed by titration with variꢀ
ous equivalents of CEES. For crystals suitable for Xꢀray analyꢀ
sis, the acetonitrile complexes were dissolved in neat CEES,
and crystallized over a period of time (ranging from a few
hours to a couple of days). All of the precursor complexes
Pd(L)(CH3CN) were fully characterized by mass spectrometry
(MS), 1H NMR spectroscopy and elemental analysis. The DMF
complex of the free ligand H2Lf, three of the acetonitrile preꢀ
cursors, and three of the CEES adducts were crystallographicalꢀ
ly characterized. The transformation equilibrium in solution
upon addition of the CEES to the acetonitrile precursors was
investigated by 1H NMR in CDCl3 (vide infra).
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Table 1. H NMR Chemical Shifts (δ, ppm)* of the Bound
CH3CN and CEES in the Complexes Pd(L)(X) (X = CH3CN
and CEES).
δ (ppm) X = CH3CN
CH3CN
X = CEES
a
b
c
d
ClCH2
ClCH2CH2 CH2 CH3 CH2CH3
2.87 2.60 1.28
Unbound 2.01
3.64
La
Lb
Lc
1.74(0.27) 3.40(0.24) 2.03(0.84) 1.83(0.77) 1.13(0.15)
1.77(0.24) 3.44(0.20) 2.06(0.81) 1.87(0.73) 1.15(0.13)
1.80(0.21) 3.46(0.18) 2.10(0.77) 1.90(0.70) 1.17(0.11)
NMR Studies
0.84(1.17) 2.83(0.81) 1.43(1.44) 1.10(1.50) 0.63(0.65)
0.80(1.21) 2.86(0.78) 1.44(1.43) 1.11(1.49) 0.66(0.62)
Le **
Lf
Solution NMR. The 1H NMR of the simplest phenylꢀ
appended Pd(La)(CH3CN) was poorly resolved and is probably
attributed to the coꢀexistence of an equilibrium between the
monomeric complex and a cyclic hexamer [Pd(La)]6 in solution
(Scheme 2 and Figure S1). Crystallographic results for crystals
isolated from the reaction mixture after sitting overnight conꢀ
firmed the formation of a hexamer, the structure and chemistry
of which was reported by us recently.20 Although the presence
of the hexamer tends to affect the resolution of the spectrum,
the signals for free and bound acetonitrile are clear and appear
at 2.01 and 1.74 ppm, respectively, for the phenyl derivative
(Table 1 and Figure S1). The upfield shifts are probably due to
the shielding effect by adjacent phenyl rings. In fact, while this
signal in the phenyl and substituted phenyl derivatives, Laꢀc (Ld
being sparingly soluble), ranges from 1.74ꢀ1.80 ppm, in the
extended aromatic naphthalene and anthracene derivatives, Le
and Lf, the signals are shifted even higher upfield by approxiꢀ
mately 1.2 and 1.7 ppm, respectively. Such an observation
tends to support the enhanced shielding in the extended π sysꢀ
tems. For Pd(Le,f)(CH3CN) clear and resolved spectra were
immediately observed upon dissolution of the sample, indicatꢀ
0.33(1.68) 2.20(1.44) 0.75(2.12) 0.32(2.28) 0.07(1.21)
*
The ∆δ values (δunbound ꢀ δbound) are shown in the brackets.
Two sets of stereoisomer signals were observed for
**
Pd(Le)(CH3CN) and Pd(Le)(CEES). In the latter, the signals were
complicated on the 400 MHz NMR spectrum, but can be clearly
elucidated by 800 MHz NMR (see Figure 3): top, cisꢀisomer A/B;
bottom, transꢀisomer C, where the average value of the two nonꢀ
equal protons CH1 and CH2 on each carbon atom is shown.
Upon stepwise addition of CEES to fresh solutions of the
complexes Pd(L)(CH3CN) in CDCl3, the proton signals of the
bound acetonitrile gradually disappeared. The signal for free
acetonitrile continued to grow upon subsequent addition of
CEES, as well as a new set of signals corresponding to coordiꢀ
nated CEES (see Supporting Information). After addition of
two equivalents of CEES, the acetonitrile complexes were alꢀ
most entirely converted to the CEES complexes (Figure 1). As
with the acetonitrile complexes, upon binding, the CEES sigꢀ
nals shifted upfield due to shielding by the aromatic rings. For
Pd(Laꢀc)(CEES) these shifts were most pronounced for the two
methylene groups coordinated with the central sulfur atom,
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b
c
CH2 and CH2 , (approximately 0.8 ppm compared to about
a
d
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0.1ꢀ0.25 ppm for CH2 and CH2 ), and the magnitude of the
chemical shift changes decreased slightly along the series R =
H > CH3 > OCH3 (Table 1). The chemical shift changes for the
naphthaleneꢀ and anthraceneꢀbased complexes, Le and Lf, inꢀ
creased dramatically, most strikingly for the anthracene derivaꢀ
tive. For the latter complex the changes are almost double
those seen in the naphthalene complex, indicating the powerful
effect of the extended π system. The NMR spectrum of the
naphthalene derivative is complicated by the presence of isoꢀ
mers as described in greater detail below.
Figure 2. Partial 1H NMR (400MHz, 298K, CDCl3) of
Pd(Le)(CH3CN). Resonance designations “▲” correspond to the
bound CH3CN signals. See Scheme 3 for the structures of the cis
and trans stereoisomers.
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Scheme 3. Possible Stereoisomers for Pd(Le)(CH3CN) and
Pd(Le)(CEES)
Upon binding CEES, the NMR spectrum of the dissymmetric
molecule becomes more complex. Theoretically, signals due to
the three stereoisomers (A, B, and C) should exist with three
distinct NMRs (Scheme 3). However, signals for only two isoꢀ
mers, cis and trans, were identified, although a three signal
pattern is observed for CEES protons CH2aꢀc. Within each of
these sets one of the three signals exhibits approximately twice
the integration as each of the other two (Figure 1d). As seen in
the higher resolution of the 800 MHz NMR spectrum (Figure
3) the signals become more resolved and are assigned to the
undifferentiated cis A/B isomer (in red) and the trans C isomer
(in magenta). The more intense set of three triplets and a quarꢀ
tet is assigned to the cis isomer. While it could be ascribed to
A and/or B, the 2D NOESY experiment shows cross peaks
between the hydrogen atoms at both the 2ꢀ and 8ꢀpositions of
the naphthalene with all four of the hydrogen atom signals on
the mustard (Figure S7). These solution structural effects, inꢀ
cluding isomerization reactions, are being investigated further.
The second set of less intense signals consists of six complex
multiplets (some of which can be recognized as octets) and one
more intense clearly defined triplet at about 0.66 ppm. The
latter signal is assigned to the terminal methyl group. The
breakdown of individual hydrogen atoms attached to the same
carbon for the other signals is a result of the diastereotopic
Cl(CH1H2)a(CH1H2)bS(CH1H2)c(CH3)d system (see inset in Figꢀ
Figure 1. Partial 1H NMR (400 MHz, 298 K, CDCl3) of
Pd(La,b,c,e,f)(CH3CN) (10 mM) after adding 2 equivalents of CEES:
(a) La, (b) Lb, (c) Lc, (d) Le and (e) Lf. Resonance designations
“∆”, “○” and “●” correspond to the signals of free CH3CN, and
free and bound CEES, respectively. See Scheme 2 for representaꢀ
tive Hꢀatom assignments.
Naphthalene Isomers. Compared with the other precursors,
the NMR spectrum of the naphthalene complexes was compliꢀ
cated by the coꢀexistence of the two stereoisomers, cis and
trans, corresponding with the two side naphthalene rings oriꢀ
ented in the same (cis) or opposite (trans) direction (Scheme
3). The possible enantiomers due to the potential planar chiraliꢀ
ty are not shown. The presence of the isomers is evident by the
observation of two signals for the bound acetonitrile methyl
group at 0.84 and 0.80 ppm. (Figure 2). Also, two independent
doublet signals at 8.46 and 8.39 ppm (denoted by * and *’)
exist for one of the naphthalene aromatic protons, each inteꢀ
grating to one proton. Other naphthalene signals are also split
but are too complex to unravel. The nearly equal integration of
the corresponding signals suggests an approximate 1:1 cis:trans
composition.
1
ure 3), which was further confirmed by a 2D Hꢀ1H COSY
experiment (Figure S6). This assignment is consistent with the
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few microliters of acetonitrile to the solution. For determination
of the binding constant, K, the relative concentration ratios of
transꢀisomer C which is C1 or no symmetry. For this isomer the
two protons on each CH1H2 group would be nonequivalent due
to the different magnetic shielding environments provided by
the trans, staggered naphthalene rings.
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3
4
the four equilibrium species in the solution were obtained by
1
integrating the representative H signals. The presence of any
hexameric species (in the case of Laꢀc) was deemed negligible
in the equilibrium solutions used for the determination of K due
to the presence of a strongly coordinating ligand (CEES).
All five pincer complexes were found to bind (K > 10)
CEES, however, the magnitude varied significantly across the
series. The pꢀCH3 (Lb) and pꢀOCH3 (Lc) substituents resulted in
only slightly increased CEES binding constants, which could
be the result of either electronic effects or possibly structural
influences of the added para substituents. However, incorporaꢀ
tion of larger aromatic rings at the pincer periphery significantꢀ
ly enhanced CEES binding (Table 2). The crystal structures of
the series of three complexes (La, Le, and Lf) shed light on this
interesting increase, which may be both electronic and structurꢀ
al in nature. The structures may also help to explain the rather
large upfield chemical shifts seen for the bound CEES in both
the naphthaleneꢀ and anthraceneꢀcontaining complexes as deꢀ
scribed in greater detail below.
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7
8
Pd*
Pd
d
9
c
d
c
H2
S
S
H1
H1
b
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H2
b
a
Cl
Cl
H1
a
H2
A/B
C
A/B : C = 46 : 54
Figure 3. Partial 800 MHz 1H NMR (298 K, CDCl3) of
Pd(Le)(CH3CN) (10 mM) with addition of ca. 2 equivalents of
CEES after reaching an equilibrium. Resonance designations “∆”
and “▲”, “○” correspond to the signals of free and bound CH3CN,
free CEES, respectively. See Scheme 3 for the complete structures
of the stereoisomers A, B and C.
Table 2. Binding Affinities (K)a of CEES with the Pincer
Complexes Pd(L)(CH3CN)
About five minutes after adding CEES to a solution of
Pd(Le)(CH3CN) in CDCl3, the concentration of cisꢀisomers is
slightly in excess compared to trans (A/B:C = 52:48). Howevꢀ
er, upon initial mixing (when the complex may not yet be comꢀ
pletely dissolved) the ratio of cis:trans isomers is considerably
higher. A slow conversion to a slight excess of transꢀisomer is
reached within ca. 2 h (Figure S8). The predominance of the
cis isomers early in the reaction may be due to the less restrictꢀ
ed approach of the mustard at the axial site away from the
naphthalenes in the anticipated associative mechanism for
square planar substitution reactions. Upon reorganization after
CEES binding, one or both of the naphthalene groups apparentꢀ
ly rotates, resulting in the different isomer ratios.
La
Lb
Lc
Le
Lf
K
15
20
25
76
220
2.34
Log K
1.16
1.31
1.39
1.88
a
1
Determined by H NMR in CDCl3. In each case three parallel
measurements were taken and an average K value is given, error <
10 %.
Crystallographic Studies
Pd(L)(CEES) Complexes. The crystal structure results of
Pd(La)(CEES) were communicated earlier,19 but the salient
features are described here for comparative purposes with the
two new crystal structures. Crystal structures were also obꢀ
tained for three of the acetonitrile precursor complexes as well
as the DMF solvate of the free base of H2Lf (see Supporting
Information).
Common trends for pincers are observed for all three of the
CEES complexes, including the rather short PdꢀN(1) distance
ranging from 1.94 to about 1.96 Å and longer bonds (by almost
exactly 0.1 Å in each case) to the amide nitrogen atoms (Table
3). The PdꢀN1 distances are longer for the mustard structures
by about 0.02 Å compared to the acetonitrile complexes, an
indication of the better trans directing capabilities of the sulfur
donor (see Table S2). The two proximal phenyl groups are alꢀ
most orthogonal to the pincerꢀPdꢀS plane for the phenyl pinꢀ
cer,19 slightly more skewed for the naphthalene complex, and
again closer to perpendicular for the anthracene host (dihedral
angles about 89o, 82o, and 87o, for the three complexes, respecꢀ
tively). These angles are all much closer to 90o than those
found for the three acetonitrile complexes (Table S2). In all
three complexes the CEES is parallel with the conjugated rings
(Figure 4). Although not shown, the bound CEES in each strucꢀ
ture exhibited “upꢀdown” disorder, with the chloroethyl and
1
Binding Studies. H NMR studies were used to investigate
electronic and steric effects of different amide substituents on
CEES binding. All the complexes were tested except
Pd(Ld)(CH3CN), which was not very soluble. Equilibrium
constants K (Eqn. 1) for the remaining five Pd(L)(CH3CN)
complexes were measured in CDCl3 (Table 2). While the
naphthalene complex, Pd(Le), consists of cis and trans isomers,
we were interested in the equilibrium constant for the entire
complex, not the individual isomers. Thus the hydrogen on the
pyridine carbon atom, C3 (Scheme 3), which was not split due
to the isomers, was used for determining the K.
CEES binds rapidly, reaching equilibrium almost immediateꢀ
ly upon mixing Pd(L)(CH3CN) and CEES in CDCl3. The equiꢀ
librium can be shifted slightly back by deliberately adding a
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ethyl arms lying in either direction, above or below, the pincer global disorder of the CEES chloroethyl and ethyl positions,
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8
plane so as to resemble an actual bound dichlorodiethylsulfide,
should just the chloroethyl positions be used for the drawings.
However, only the component with a higher occupancy is
shown in Figure 4 except for the naphthalene complex (vide
infra). What is striking is the increased linear alignment of the
mustard surrogate along the aromatic skeleton progressing
across the phenyl, naphthalene, anthracene series (Figure 4b, d,
f, and h).
the cis isomer could be either A or B. What is shown in Figure
4c,d is the A isomer, since for both the CEES and the pincer
portions of the complex, those were the positions with the
highest occupancy. Interestingly, the predominant cis form in
terms of atom occupancy is opposite to what is identified as the
more stable isomer, i.e., trans, in solution over time.
Table 3. Coordinated Bond Distances (Å) and Dihedral Angles
9
(°) for the NNNꢀPdꢀCEES Pincer Complexes
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Pd(Le)(CEES)
(a)
(b)
Pd(La)(CEES)
Pd(Lf)(CEES)
A/B
C
Pd N1
Pd N2
Pd N3
1.940(11)
2.040(9)
2.029(9)
1.957(5)
2.051(6)
2.105(8)
2.318(6)
1.953(5)
2.049(6)
2.076(8)
2.300(9)
1.954(3)
2.054(3)
2.060(3)
2.326(17)
Pd S(CEES) 2.302(4)
∠Pl(NNNPd)
ꢀ
88.3, 89.8
81.0, 83.1 79.8, 85.8 86.7, 86.8
a
Pl(Ar)
a The angle is defined as the dihedral angle between the side aroꢀ
matic ring averaged plane and the N(1)N(2)N(3)ꢀPd pincer averꢀ
aged plane.
(c)
(d)
The alignment of the mustard with the naphthalene rings in
Pd(Le)(CEES) becomes much more apparent compared to the
phenyl derivative, Pd(La)(CEES) (Figure 4cꢀf, and a and b,
respectively). However, while the naphthalene falls short of
covering the entire surrogate mustard chain, as seen in both
Figure 4d and f the chlorine atom wraps up toward the palladiꢀ
um, forming a relatively close contact, 3.10 and 3.16 Å for the
A and C isomers, respectively (PdꢁꢁꢁCl van der Waals is about
3.4 Å).21 This proximity, albeit not an actual bond, constitutes a
second interaction of the bound mustard, in addition to the Pdꢀ
S bond (or possibly a third interaction if the weak van der
Waals attractions with the naphthalene rings are considered).
However, it may just be a reflection of the naphthalene orientaꢀ
tions, or just happenstance. Nonetheless the PdꢀꢀꢀCl interaction
may be in part responsible for the significantly enhanced bindꢀ
ing constant compared to the phenyl and phenylꢀsubstituted
complexes if it is indeed present in solution.
As anticipated, Pd(Lf)(CEES) has the same general coordinaꢀ
tion sphere as the other complexes (Figure 4g and h, Figure 5,
and Table 3), although it too suffers from some disorder (see
Supporting Information). Additionally there is a free CEES of
solvation within the crystal lattice that exhibits extreme disorꢀ
der across the crystallographic inversion center, and which
resisted all attempts at modeling. Its presence does not, howꢀ
ever, detract from the overall validity of the structure of the
palladium complex. Clearly, in the anthracene derivative, the
extended aromatic rings are beautifully positioned for aligning
with the entire length of the mustard carbon chain, with only
the chlorine atom poking outside the wall. All the protons on
the CEES chain have a short contact with the closest anthraꢀ
cene ring plane (Cꢁꢁꢁπ plane distances varying between 3.4ꢀ3.5
Å) indicating the presence, at the very least, of van der Waals
interactions.
(e)
(f)
(g)
(h)
Figure 4. ORTEP drawings at 50% ellipsoid probability and side
views showing the bound CEES (space filling) “shielded” by the
aromatic walls: Pd(La)(CEES) (a, b); Pd(Le)(CEES) (major speꢀ
cies A (c, d), minor species C (e, f)); and Pd(Lf)(CEES) (g, h).
Nonessential solvent and water molecules are omitted for clarity.
The structure of Pd(Le)(CEES) was complicated because of
the coꢀcrystallization of the possible isomers, A/B and C
(Scheme 3), which appeared as disordered atomic positions.
Upon unravelling the disorder, the two isomers, A/B and C,
emerged at about 56 and 44% occupancy, respectively (Figure
4cꢀf, Table 3, and Supporting Information). Because of the
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Each Pd(Lf)(CEES) complex is adjacent to a neighboring
complex, forming a dimer pair with the two CEES chains oriꢀ
ented in opposite directions (Figure 5a). The wallꢀlike effects
of the anthracene groups then extend throughout the crystal
lattice (Figure 5b and c). These findings, that the incorporation
of larger aromatic rings results in improved binding affinity as
well as the solid state formation of the extended wall channels,
can be potentially expanded to other pseudoꢀlinear targets.
isomerization may be occurring in solution, but also that the
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mechanism might proceed via a preferred CEES addition to the
cis rather than trans precursor complex. These results are curꢀ
rently being explored further.
This study has thus shed light on detailed structural and
mechanistic aspects of the binding of pseudoꢀlinear molecules
with square planar pincer complexes. While structural comꢀ
plementarity in terms of hostꢀguest interactions has long been
known, the clearly identified wall effect observed with the
mustard surrogate may lead to new applications of wallꢀ
building in sensing, separations, and transport of other target
molecules and ions.
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(a)
(b)
ASSOCIATED CONTENT
Supporting Information. Crystallographic data in CIF format.
Synthetic procedures and spectral characterization of compounds,
NMR studies and crystallographic information. This material is
available free of charge via the Internet at http://pubs.acs.org.
(c)
AUTHOR INFORMATION
Corresponding Author
kbjames@ku.edu
ACKNOWLEDGMENT
This project received support from the Defense Threat Reduction
AgencyꢀJoint Science and Technology Office for Chemical and
Biological Defense (B104283I). The authors also thank the Naꢀ
tional Science Foundation, CHEꢀ0923449 for purchase of the Xꢀ
ray diffractometer. We also thank Dr. J. T. Douglas for NMR techꢀ
nical assistance and helpful discussion.
Figure 5. Views of the complex Pd(Lf)(CEES): (a) fourꢀwalled
anthracene enclosure of a single dimer pair and (b) overhead and
(c) side views of the infinite fourꢀwalled channel holding antiꢀ
parallel headꢀtoꢀtail CEES chains.
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The goal of this project was to examine the influence of peꢀ
ripheral groups attached to NNN pincer complexes of Pd(II) on
the binding of the pseudoꢀlinear sulfur mustard surrogate
CEES. The ligands are readily synthesized by an efficient, high
yield two step reaction, followed by complexation with pallaꢀ
dium(II). The acetonitrile complexes were found to bind CEES,
rapidly forming an equilibrium between free and complexed
guest. The high affinity of the palladium complexes for CEES
was anticipated due to the soft nature of both the palladium and
sulfur atoms, in keeping with HardꢀSoftꢀAcidꢀBase concepts.
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interactions of the CEES with the pincer framework that led to
a surprising range of values for the equilibrium constants.
While simple substituents on the side phenyl rings resulted
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more extended aromatic rings, e.g. naphthalene and anthracene,
provided more rigid structural “walls” to enclose the pseudoꢀ
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15-fold increased binding affinity (K) for CEES
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